Pulmonary Metastases - Symptoms, Diagnosis, and Treatment

Introduction

The term metastasis represents the spread of cancer cells from the primary tumor (site of origin of cancer) to the surrounding tissues and organs as well as to distant sites. The lung is the second most common site for metastasis, with the incidence of synchronous pulmonary metastases being about 18 per 100,000 and is slightly higher in men than women. About 24 to 50 percent of cancers occurring elsewhere in the body are estimated to have metastatic deposits in the lungs. Incidence increases with age. Metastasis can occur in structures near the tumor or spread to unrelated and faraway locations. Metastasis that is diagnosed at the same time of initial cancer presentation is termed synchronous metastasis, and metastasis occurring after the initial cancer staging is termed metachronous metastasis. Microscopic study of metastatic cells shows that the cells are similar to that of primary cancer and not the cells present at the site of metastasis. The tendency of a tumor to metastasize depends on its type, behavior, and growth rate; metastasis is considered a feature of advanced cancer stages in most cases.

What Are the Cancers Commonly Associated With Lung Metastases?

Cancer from any part of the body has the probability of spreading to the lungs. Some of the cancers most commonly associated with lung metastasis include:

• Breast cancer.

• Ovarian cancer.

• Uterine cancer.

• Any head and neck cancer.

• Bladder cancer.

• Testicular cancer.

• Kidney cancer.

• Colorectal Cancer.

• Pancreatic cancer.

• Thyroid cancer.

• Sarcoma, lymphoma, melanoma, etc.

How Does Cancer Spread to the Lungs?

According to Paget’s seed and soil hypothesis, the ability of a tumor cell to proliferate is essential to establish metastatic growth in a distant site. The mode and site to which a tumor spreads are largely dependent on the genetic, pathologic, and histologic characteristics of the primary tumor. Three main mechanisms by which the spread of cancer to the lungs can occur include:

1. Lymphatic Spread - Involves spreading of tumor cells through the lymphatic system that consists of the lymph (a mixture of immune cells and fluid flowing through a network of vein-like vessels in the body) and several lymph nodes that form a network. Tumor cells that break off from the primary tumor are carried through the lymphatics to distant sites. Tumors invariably invade the lymph nodes, which are often the first site of metastasis in many cancers. Lymph nodes are invaded in order of the draining or sentinel node (which is the nearest to the primary tumor) and then to the more distal nodes. Tumor cells spreading through lymph also enter the venous blood since the lymphatics drain into the venous circulation through the thoracic duct or the right lymphatic duct, followed by the subclavian veins. Two ways of lymphatic spread to the lungs possible are either antegrade lymphatic invasion through the diaphragm and pleural surfaces or a retrograde spread from the hilar nodes.

2. Hematogenous Spread - The seeding of tumor cells is thought to occur due to the circulation of the cells in the blood. The detached tumor cells travel through the blood and are taken to different sites. It can occur separately or in combination with lymphatic spread. It is common in cancers with venous drainage into the lungs, such as tumors in the thyroid, head and neck, kidney, testes, adrenals, osteosarcoma, etc. Sometimes a direct spread to the pleura may occur.

What Are the Symptoms of Pulmonary Metastases?

Individuals may remain asymptomatic until nodules in the lungs are found incidentally. Systemic symptoms such as fatigue, loss of appetite, weight loss, nausea, etc. may be present. Other localized symptoms include:

• The cough may be productive (with sputum) or non-productive (dry).

• Difficulty in breathing (dyspnea).

• Coughing up blood (hemoptysis).

• Chest pain.

• Vomiting.

• Lower back pain.

• Disturbance in body electrolytes.

• Pleural effusion may occur.

What Are Some Diagnostic Investigations of Pulmonary Metastases?

Individuals may have a history of a known primary tumor or may present with metastases initially itself. Pulmonary metastases can occur in the form of solitary or multiple metastases. Physical examination may reveal wheezing in the presence of a bronchogenic mass, crackles in the presence of fluid in the alveoli, and decreased breath sounds in case of pleural effusion. Clubbing in the digits, weight loss, lymphadenopathy, and signs of superior vena cava syndrome may also be present.

Imaging tests used in the diagnosis of pulmonary metastases include:

• Chest X-Ray - Metastatic deposits appear as multiple nodules that are rounded and peripheral, scattered throughout the lungs.

• Computed Tomography (CT) - CT is a great tool to visualize metastatic nodules. The nodules appear to be well-circumscribed and are generally present peripherally. Different patterns may be present in different cancers; for example, small diffuse and innumerable metastases (military pattern) occur in the cases of thyroid carcinoma and osteosarcoma, whereas malignant melanoma presents with a large singular metastatic mass. Calcification or consolidation of the metastases may occur.

• Positron Emission Tomography (PET): PET with fluorodeoxyglucose (FDG) is used to detect metastasis elsewhere in the body. PET-CT is used for the precise location of metastasis superimposed on a CT scan.

• Bronchoscopy.

• Lung needle biopsy.

• Cytological examination of the sputum or pleural fluid may be done.

What Is the Treatment of Pulmonary Metastases?

Tumors with pulmonary metastasis are generally designated as stage IV. Often a combination of treatment modalities rather than a stand-alone treatment is administered. The treatment choice is made based on the underlying tumor pathology, immunohistopathology, etc.

1. Chemotherapy - Chemotherapy is not curative for lung metastases, but for a few tumors like germ cell testicular tumors, which are treated with cis-platin resulting in a high long-term cure rate. Osteogenic sarcomas are responsive to chemotherapy. Neoadjuvant drugs like Methotrexate, Cisplatin, Doxorubicin, and Ifosfamide, etc., help prevent systemic metastasis. Preoperative chemotherapy resulted in the resolution of lung nodules in about one-third of cases. Adjuvant chemotherapy postoperatively also resulted in improved survival rates. However, the side effects of chemotherapy are well known. Some of them include nausea, hair loss, loss of appetite, weight loss,

2. Immunotherapy - It involves stimulating the immune system which improves its natural ability to fight cancer. Some tumors are highly immunogenic and respond well to immunotherapy, such as renal cell carcinoma, malignant cutaneous melanoma, etc.

3. Radiation - Radiation may increase the expression of major histocompatibility complex (MHC) class I and II molecules on the tumor cells and tumor antigenic markers, facilitating the immune system to step up antitumor activity and T-cell-mediated tumor immunity.

What Is the Prognosis of Pulmonary Metastases?

The clinical prognosis and treatment options in individuals with pulmonary metastases can be very different from that of the primary tumor of origin. The survival rates vary widely with the degree of lung involvement, nature, and deference of the primary tumor to treatment, etc. A cancer cure at this stage is out of the question, and palliative care can preserve the quality of life.

Conclusion

Metastasis is the spread of cancer from its site of origin into surrounding structures or distant sites. The lungs are a common site for metastasis in many different cancers. The metastatic spread occurs either through the bloodstream or the lymphatic system. Pulmonary metastases may present in the case of a known primary tumor or maybe the initial finding, which leads to probing for the primary tumor. Spread to the lungs is an adverse prognostic sign. However, the specific prognosis depends on the site and extent of the spread of the primary tumor. Treatment options available include chemotherapy, radiotherapy, immunotherapy, and surgery. Treating pulmonary metastases requires interdisciplinary collaboration between oncologists and other specialists such as radiation oncologists, pathologists, pulmonologists, cardiothoracic surgeons, etc. Palliative care to treat symptoms as and when they arise is also adopted.